Burkholderia pseudomallei: Infectious substances Pathogen Safety Data Sheet

Section I: Infectious agent

Name

Burkholderia pseudomallei

Agent type

Bacteria

Taxonomy

Family

Burkholderiaceae

Genus

Burkholderia

Species

pseudomallei

Synonym or cross reference

Bacillus pseudomallei, Malleomyces pseudomallei, Pseudomonas pseudomallei ^{Footnote 1} and melioidosis ^{Footnote 2}.

Characteristics

Brief description

Burkholderia pseudomallei is a motile, aerobic, non-spore forming, Gram-negative bacillus ^{Footnote 2}. It exhibits bipolar staining when stained with methylene blue or Wright's stain, resembling a safety pin ^{Footnote 2}. B. pseudomallei is pleomorphic, occasionally forming chains, and appears as "wrinkled" colonies on agar media ^{Footnote 3 Footnote 4}.

Properties

As an environmental saprophyte, B. pseudomallei can use at least 80 different compounds as a carbon source ^{Footnote 5}. The bacterium can persist over a wide range of pH values and salt concentrations, survive desiccation, and may survive exposure to chlorine at levels commonly used for water treatment ^{Footnote 3 Footnote 6}. These factors allow B. pseudomallei to remain viable for extended periods in the environment, thereby increasing the likelihood of human and animal exposure.

Section II: Hazard identification

Pathogenicity and toxicity

B. pseudomallei is the causative agent of melioidosis, a disease which affects humans and animals. Melioidosis in humans has varied clinical presentations with pneumonia (dyspnea and productive cough), bacteremia (high fever and malaise), internal organ abscesses (most often prostate, spleen, liver and kidney) and localized soft tissue or joint abscesses being the most common ^{Footnote 7}. Rarer presentations include osteomyelitis, septic arthritis, and central nervous system involvement ^{Footnote 7 Footnote 8}. Clinical signs of neurological illness include fever, headache, cranial nerve palsy, weakness, ataxia, seizures, decreased consciousness, and flaccid paralysis ^{Footnote 7}. Clinical presentation varies depending on the route of infection, inoculum dose, strain virulence, and host factors ^{Footnote 7}. Serological evidence suggests that most exposures do not result in the development of disease, with one study reporting only 1 in 4,600 seroconversion-associated exposures resulted in clinical disease ^{Footnote 7 Footnote 9}. In recent years, the reported mortality rate for melioidosis ranges from approximately 14 to 50%, and varies depending on the time to diagnosis and treatment ^{Footnote 10 Footnote 11 Footnote 12 Footnote 13 Footnote 14}.

In animals, melioidosis is most commonly reported in sheep, goats and swine ^{Footnote 15}. Clinical signs of melioidosis can vary, with acute fulminate septicaemia, local infection, subacute illness, chronic infection and subclinical disease all possible. Common symptoms in herbivores are dyspnoea, nasal discharge, emaciation, hyper-salivation and lameness; while in non-human primates, high fever, lymphadenopathy, lethargy and respiratory distress are common ^{Footnote 16}. In dogs, acute disease presents with fever, diarrhea, pneumonia and septicemia, whereas chronic illness typically involves abscess formation ^{Footnote 15}.

Predisposing factors

Common co-morbidities associated with B. pseudomallei infection include diabetes (39%), excessive alcohol use (39%), chronic lung disease (26%), hypertension (15%), chronic renal disease (12%), and immunosuppression (8%) ^{Footnote 11 Footnote 12 Footnote 14}. Daily activities associated with B. pseudomallei infection include working in a rice field, exposure to soil and water, having an open wound, eating food contaminated with dirt or dust, drinking untreated water and exposure to rain or water inhalation ^{Footnote 17}. A link between extreme weather events with high rainfall and clusters of B. pseudomallei infections has been observed ^{Footnote 18}. Nosocomial outbreaks, although rare, have also been reported ^{Footnote 19}.

Communicability

B. pseudomallei is common in soil and surface water in endemic areas, and both humans and animals are typically infected through exposure of damaged skin or mucous membranes to contaminated dust, soil, or water ^{Footnote 15 Footnote 17 Footnote 20}. Infection may also occur through inhalation, ingestion, or laboratory-related exposure ^{Footnote 20}. Arthropods are not known to be involved in the transmission of melioidosis, although experimental evidence suggests it is plausible ^{Footnote 21 Footnote 22}. Human-to-human transmission is rarely reported and primarily occurs between a mother and child during breastfeeding or at birth ^{Footnote 23 Footnote 24 Footnote 25}. Human-to-human transmission of melioidosis was suspected between siblings with cystic fibrosis ^{Footnote 26} and siblings with diabetes ^{Footnote 27}.

Epidemiology

B. pseudomallei is endemic in Southeast Asia and Northern Australia, but it is considered an emerging infectious disease in most tropical countries ^{Footnote 28}. Cases of infection have been reported in Sub-Saharan Africa, Latin America and the Caribbean, South America, and the Middle East. Globally, it is estimated that 165,000 human melioidosis cases occur annually, resulting in 89,000 deaths ^{Footnote 28}. These estimates suggest that melioidosis is substantially underreported and may be endemic in up to 79 countries.

Host range

Natural host(s)

B. pseudomallei can infect humans as well as a very large range of animal species. Infection has been reported in livestock such as sheep, goat, pig, cattle and horses ^{Footnote 29 Footnote 30}, and in captive zoo animals such as camels, non-human primates, bison, deer, zebras, cheetahs, badgers and kangaroos ^{Footnote 31}. B. pseudomallei infection has also occurred in aquatic animals, specifically cetaceans, sea lions and crocodiles ^{Footnote 31 Footnote 32 Footnote 33}. Infection of common pets such as cats and dogs has been reported, although they appear more resistant to infection ^{Footnote 29}.

Other host(s)

Laboratory mice, guinea pigs, rats and monkeys are commonly used in experimental animal models of melioidosis ^{Footnote 34 Footnote 35}.

Infectious dose

The minimum infectious dose is unknown for humans ^{Footnote 3}. Infection in a murine model of chronic melioidosis was achieved through intranasal inoculation with 100 colony-forming units (CFU) ^{Footnote 36}.

Incubation period

Most patients experience acute disease with symptom onset occurring an average of 9 days post-exposure (range 1-21 days) ^{Footnote 37}. However, in as many as 4% of cases, infection can remain latent for years ^{Footnote 12 Footnote 37} or decades ^{Footnote 38} prior to reactivation and development of symptomatic disease.

Section III: Dissemination

Reservoir

In endemic regions B. pseudomallei is often found associated with grasses and therefore herbivores who feed on these grasses can be reservoirs ^{Footnote 39}. B. pseudomallei can spread both from the droppings of these animals and importation of infected animals.

Zoonosis/Reverse zoonosis

Rare cases of zoonotic transmission from animals to humans have occurred ^{Footnote 29}.

Vectors

Arthropods are not known to be involved in the transmission of melioidosis, although experimental evidence suggests it is plausible ^{Footnote 21 Footnote 22}.

Section IV: Stability and viability

Drug susceptibility

Usually susceptible to ceftazidime, chloramphenicol, doxycycline, trimethoprim-sulfamethoxazole ^{Footnote 7}, amoxicillin-clavulanate, ureidopenicillins (azlocillin and piperacillin), and carbapenems (imipenem and meropenem) ^{Footnote 40}.

Drug resistance

Resistant to penicillins, cephalosporins, macrolides, rifamycins, and aminoglycosides ^{Footnote 7 Footnote 40}. Although less frequent, some isolates also show resistance to doxycycline, tetracycline, ceftazidime, sulfonamides, amoxicillin-clavulanic acid, and carbapenems ^{Footnote 40 Footnote 41}.

Susceptibility to disinfectants

Exposure to 1 mg/L chlorine for 30 minutes led to 99.99% reduction of B. pseudomallei ^{Footnote 42}.

Physical inactivation

B. pseudomallei can be inactivated by exposure to 4.65 W/m² of UV radiation (254 nm) for 7.75 minutes ^{Footnote 3}. Loss of apparent viability can be greater than 80 to 90% after 24 h at 0°C ^{Footnote 3}. B. pseudomallei is also reported to be susceptible to inactivation by sunlight ^{Footnote 43}.

Survival outside host

B. pseudomallei can survive for several months in surface water and rice paddy fields, up to 36 months in soil or in distilled water under laboratory conditions at tropical room temperature, and for years in triple distilled water ^{Footnote 2 Footnote 12}.

Section V: First aid/medical

Surveillance

The gold standard for diagnosis of B. pseudomallei infection is bacterial culture. This method, although having 100% specificity, is reported to have an estimated sensitivity of 60.2% ^{Footnote 44}. Numerous quantitative polymerase chain reaction (qPCR)-based detection methods are under development but are not yet commonly used in clinical practice ^{Footnote 45}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

The standard of care for human melioidosis involves an initial treatment with either intravenous ceftazidime (50 mg/kg) or meropenem (50 mg/kg) every 6-8 hours for 2-6 weeks depending on disease severity ^{Footnote 7}. This initial phase is followed by a 3-6 month eradication phase using the oral antibiotic trimethoprim-sulfamethoxazole. Use of granulocyte colony-stimulating factor is recommended for patients who develop septic shock. Infected animals are often culled rather than treated ^{Footnote 15}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

No vaccines are available to date ^{Footnote 46}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

Post-exposure prophylaxis with a 21-day course of trimethoprim-sulfamethoxazole may be recommended for at-risk populations, laboratory exposures and in the case of intentional release as a biological weapon ^{Footnote 7 Footnote 45 Footnote 47}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI: Laboratory hazards

Laboratory-acquired infections

Eight cases (no fatalities) of laboratory-acquired B. pseudomallei infection were reported prior to 1976 ^{Footnote 48}. In one of these cases, the affected individual cleaned a centrifuge spill of B. pseudomallei culture with bare hands ^{Footnote 49}. An additional well-described case of laboratory-acquired melioidosis was reported in 1981 ^{Footnote 50}; the laboratory worker was presumably exposed to infectious aerosols during open-flask sonication of B. pseudomallei culture on an open lab bench ^{Footnote 51}.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline on notification and reporting procedures is also available.

Sources/specimens

Abscesses, wound exudates, pus, sputum, throat swabs, blood, urine, faeces, and various other tissues ^{Footnote 2 Footnote 12 Footnote 6}

Primary hazards

Direct contact with cultures or infectious materials from humans, animals or the environment; ingestion; autoinoculation; and exposure to infectious aerosols or droplets ^{Footnote 49 Footnote 51}.

Special hazards

Soil and water samples from endemic areas may pose a risk of infection ^{Footnote 49}.

Section VII: Exposure controls/personal protection

Risk group classification

B. pseudomallei is a Risk Group 3 human pathogen and Risk Group 3 animal pathogen and is also a Security Sensitive Biological Agent (SSBA) ^{Footnote 52}.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures. Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard to be followed. At minimum, it is recommended to use full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Section VIII: Handling and storage

Spills

Allow aerosols to settle. Wearing protective clothing, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the infectious agent must be completely decontaminated before they are removed from the containment zone. This can be achieved by using a decontamination method that has been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Containers of infectious material stored outside the containment zone must be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

SSBA: Inventory of Risk Group 4 (RG4) pathogens and security sensitive biological agents (SSBA) in long-term storage to be maintained and to include:

• specific identification of the pathogens, toxins, and other regulated infectious material; and
• a means to allow for the detection of a missing or stolen sample in a timely manner

Section IX: Regulatory and other information

Canadian regulatory context

Controlled activities with B. pseudomallei require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada ^{Footnote 53}. The following is a non-exhaustive list of applicable designations, regulation, or legislation:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations
• Annually Notifiable Disease (animal)

Updated

September 2021

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosecurity Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright^© Public Health Agency of Canada, 2021